Identification and functional analysis of osmosensitive ion channels responsible for the regulation of vasopressin secretion.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06778
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: Akita University
• Principal Investigator: Kaori Sato (佐藤かお理) 秋田大学, 医学系研究科, 助教 (60614196)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: イオンチャネル / アニオンチャネル / LRRC8ファミリー

Outline of Final Research Achievements

The expression of membrane proteins that may be involved in taurine-induced membrane depolarization and inhibition of spontaneous firing activity in vasopressin neurons under hypo-osmotic conditions has identified alpha, beta and gamma forms of GABAA receptors.
The volume-sensitive anion channel VSOR, which is activated following volume expansion of vasopressin neurons by hypoosmotic stimulation, is known to be composed of a hexamer of 8B-8E combinations with a core of LRRC8A. Analysis of these combinations using patch-clamp and cross-sectional area measurements in gene-knockdown and overexpressing cells suggested that not only 8A but also 8D plays an important role in the volume recovery mechanism after cell expansion due to hypoosmotic pressure.

Free Research Field

生理学

Academic Significance and Societal Importance of the Research Achievements

学術的意義は、これまで未解明であったAVP分泌調節メカニズムの初動装置としての浸透圧検知性イオンチャネルの分子同定と機能解明を世界に先駆けて行う点にある。これによって解明されるAVPニューロン独自の細胞容積調節メカニズムや分泌調節メカニズムが、今後OXTニューロンを含む多くの分泌細胞における容積調節メカニズムや分泌調節メカニズムの研究の発展にも貢献できる。更には、本研究課題により同定されたイオンチャネルは、指定難病である下垂体性ADH分泌異常症の新たな治療法開発のターゲットを与えることが期待できる。